N-substituted piperazines

ABSTRACT

Novel N-alkyl substituted piperazines have been discovered, which are useful as insecticides or fungicides. Such compounds are of Formula (I) 
     
       
         
         
             
             
         
       
         
         
           
             wherein X, Y, R1 and R2 are as defined herein.

This application claims the benefit of U.S. Provisional Application No.60/695,364, filed on Jun. 30, 2005, the entire contents of which ishereby incorporated by reference. Additionally, this application claimsthe benefit of U.S. Non-provisional application Ser. No. 11/479,772,filed 30 Jun. 2006, the entire contents of which is hereby incorporatedby reference. The present invention relates to novel N-alkyl substitutedpiperazines and their use as fungicides and insecticides.

BACKGROUND OF THE INVENTION

Various piperazine derivatives have been disclosed in references such asWO 2004/060865, WO 97/26252, WO 01/46166, JP8-26995, JP63-141966, U.S.2003/0044845, U.S. Pat. No. 6,011,035 and U.S. Pat. No. 6,387,897.However, these references do not disclose the piperazine derivatives ofthe present invention.

Additionally, there continues to be a need for additional insecticidaland fungicidal compounds, due to the continual development of resistanceto the insecticides and fungicides currently used in the field. Forexample, there are at least 400 species of arthropods which areresistant to one or more insecticides. Therefore, the need continues todevelop new insecticides and fungicides, and particularly for compoundsthat have new or atypical modes of action.

SUMMARY OF THE INVENTION

The present invention relates to compounds of Formula (I)

wherein

X and Y are each independently selected from the group consisting of adirect bond, alkyl, carbonyl, carbonylalkyl, carbonylalkylether,carboxylalkyl, alkylcarbonyl, alkylcarboxyl, and alkylether;

-   -   with the proviso that both X and Y cannot be a direct bond; and        when either X or Y is a direct bond, then the R1 or R2        associated with that bond is not phenyl or optionally        substituted phenyl; and        R1 and R2 are each independently selected from the group        consisting of:

alkyl;

aryl, optionally substituted with cyano, alkoxy, halogen, alkylhalo,alkoxyhalo, carboxylalkyl, carbonylalkyl, benzyloxy, nitro, benzoyl,phenyl, carboxamido, or heteroaryl;

heteroaryl, optionally substituted with aryl, heteroaryl, alkyl,halogen, alkylhalo, alkoxy, cycloalkyl or cyano;

cycloalkyl, optionally substituted with alkyl or halogen; and

a heterocyclic ring, optionally substituted with alkyl.

The present invention also relates to insecticidal or fungicidalcompositions thereof and methods of use.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the compounds of Formula (I),compositions thereof and their use as insecticides and fungicides, inaccordance with the definitions herein. In relation to the definitionshereafter, R is an alkyl group; X refers to a halogen atom, and thesymbol ‘*’ denotes the point of attachment.

The term “alkoxy” refers to an alkyl group, attached through an oxygenatom, e.g. *—OR.The term “alkoxyhalo” refers to an alkoxy group which is substitutedwith one or more halogens (*—O—R—X_(n)).The term “alkyl” (including derivative terms such as alkoxy) as usedherein includes straight and branched chains containing from 1 to 6carbon atoms. Thus, typical alkyl groups are methyl, ethyl,1-methylethyl, propyl, and 1,1-dimethylethyl, and the like.The term “alkylcarbonyl” refers to an alkyl group attached to a carbonyl(*—R—C(O)—).The term “alkylcarboxyl” refers to an alkyl group attached to a carboxylgroup (*—R—C(O)—O—).The term “alkylether” refers to an alkyl group attached to an oxygen(*—R—O—).The term “alkylhalo” refers to an alkyl group which is substituted withone or more halogens (*—R—X_(n)).The term “aryl” refers to a mono or bicyclic aromatic ring, such asphenyl or naphthalene.The term “benzodioxane” refers to a 10 membered, fused, bicyclicaromatic ring containing two oxygen atoms in the para position of thesecond, 6-membered, non-aromatic ring, i.e. a benzene ring fused to adioxane ring.The term “benzodioxole” refers to a 9 membered, fused, bicyclic aromaticring containing two non adjacent oxygen atoms in the second,five-membered, non-aromatic ring, i.e. a benzene ring fused to a dioxolering.The term “benzothiophene” refers to a 9 membered, fused, bicyclicaromatic ring containing one sulfur atom, i.e. a benzene ring fused to athiophene ring.The term “benzoyl” refers to a carbonyl group attached to a phenyl group(*—C(O)-phenyl).The term “benzyloxy” refers to a benzyl group attached to an oxygen atom(*—O—CH₂-phenyl).The term “carbonyl” refers to a carbon atom double bonded to an oxygenatom (*—C(O)—).The term “carbonylalkyl” refers to a carbonyl group attached to an alkylgroup (*—C(O)—R—).The term “carbonylalkylether” refers to a carbonyl group attached to analkylether group (*—C(O)—R—O—).The term “carboxamido” refers to a carbonyl group attached to an aminogroup (*—C(O)—NH₂).The term “carboxylalkyl” refers to a carboxyl group attached to an alkylgroup (*—C(O)—O—R—).The term “cyano” refers to a carbon atom triple bonded to a nitrogenatom (*—C≡N).The term “cycloalkyl” refers to a saturated C3-C6 membered ring, such ascyclobutane, cyclopropane, cyclohexane and the like.The term “halogen” or “halo” refers to the atoms fluorine, chlorine,bromine, and iodine.The term “heteroaryl” refers to a 5 or 6 membered unsaturated ringcontaining one, two or three heteroatoms, preferably one or twoheteroatoms independently selected from oxygen, nitrogen and sulfur; orto a bicyclic unsaturated ring system containing up to 11 atomsincluding one, two or three heteroatoms selected from oxygen, nitrogenand sulfur. Examples of heteroaryl ringss include, but are not limitedto, 2-, 3- or 4-pyridine, pyrazine, pyrazole, 2-, 4-, or 5-pyrimidine,2- or 3-thiophene, 2- or 3-furan, oxazole, quinoline, benzofuran,benzopyronye, benzothiophene, thiophenepyrazoline, thiadiazole,benzodioxane, benzodioxole, indole, pyridazine, triazole, imidazole,pyrrole, isoxazole, thiazole, isothiazole, oxadiazole, thiadiazoleisoquinoline and the like. The ring may be attached at any position solong as the laws of chemical valency and stereochemistry are observed.The term “heterocyclic” refers to a 3 to 5 membered, saturated ringcontaining 1-3 heteroatoms selected from oxygen, nitrogen or sulfur;such as oxirane, pyrrolidine, morpholine rings and the like. The ringmay be attached at any position so long as the laws of chemical valencyand stereochemistry are observed.The term “nitro” refers to a nitrogen atom bonded to two oxygen atoms,(*—NO₂).The term “oxazole” refers to a 5 membered, aromatic ring containing oneoxygen atom and one nitrogen atom, non-adjacent to each other, i.e. anoxazole ring.The term “oxirane” refers to a 3 membered ring containing oxygen andcarbon, i.e.

The term “pyrazine” refers to a 6 membered, aromatic ring containing 2nitrogen atoms, wherein the N's are in the para position.The term “pyrazole” refers to a 5 membered, aromatic ring containing 2nitrogen atoms, wherein the N's are adjacent to one another.The term “thiadiazole” refers to a 5 membered, aromatic ring containingtwo nitrogen atoms and a sulfur atom.The term “thiophenepyrazoline” refers to a 8 membered, fused, bicyclicaromatic ring containing one sulfur atom, and two nitrogen atoms,wherein the sulfur atom is part of a thiophene ring and the nitrogenatoms are part of a pyrazoline ring fused therewith.

In one embodiment of the present invention X and Y are eachindependently selected from the group consisting of a direct bond,alkyl, and carbonyl;

-   -   with the proviso that both X and Y cannot be a direct bond; and        when either X or Y is a direct bond, then the R1 or R2        associated with that bond is not phenyl or optionally        substituted phenyl; and        R1 and R2 are each independently selected from the group        consisting of:

aryl, optionally substituted with cyano, alkoxy, halogen, alkylhalo,alkoxyhalo, carboxylalkyl, carbonylalkyl, benzyloxy, nitro, benzoyl,phenyl, carboxamido, or heteroaryl; and

heteroaryl, optionally substituted with aryl, heteroaryl, alkyl,halogen, alkylhalo, alkoxy, cycloalkyl or cyano.

The compounds of the present invention can exist as one or morestereoisomers. The various stereoisomers include geometric isomers,diastereomers and enantiomers. Thus the compounds of the presentinvention include racemic mixtures, individual stereoisomers andoptically active mixtures. It will be appreciated by those skilled inthe art that one stereoisomer may be more active than the others.Individual stereoisomers and optically active mixtures may be obtainedby selective synthetic procedures, by conventional synthetic proceduresusing resolved starting materials or by conventional resolutionprocedures.

The compounds of the present invention can be prepared by known methodsin the art as outlined in the examples of the present specification.

Another aspect of the present invention relates to an insecticidal orfungicidal composition comprising a compound of Formula (I) and aphytologically-acceptable inert carrier. The compositions are typicallyeither concentrated formulations which are dispersed in water forapplication, or are dust or granular formulations which are appliedwithout further treatment. The compositions are prepared according toprocedures and formulae which are conventional in the agriculturalchemical art, but which are novel and important because of the presencetherein of the compounds of this invention. Some description of theformulation of the compositions will be given, however, to assure thatagricultural chemists can readily prepare any desired composition.

The dispersions in which the compounds are applied are most oftenaqueous suspensions or emulsions prepared from concentrated formulationsof the compounds. Such water-soluble, water-suspendable or emulsifiableformulations are either solids, usually known as wettable powders, orliquids usually known as emulsifiable concentrates or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the activecompound, an inert carrier, and surfactants. The concentration of theactive compound is usually from about 10% to about 90% by weight. Theinert carrier is usually chosen from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among the sulfonated lignins, thecondensed naphthalenesulfonates, the naphthalenesulfonates, thealkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactantssuch as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenientconcentration of a compound, such as from about 50 to about 500 gramsper liter of liquid, equivalent to about 10% to about 50%, dissolved inan inert carrier which is either a water miscible solvent or a mixtureof water-immiscible organic solvent and emulsifiers. Useful organicsolvents include aromatics, especially the xylenes, and the petroleumfractions, especially the high-boiling naphthalenic and olefinicportions of petroleum such as heavy aromatic naphtha. Other organicsolvents may also be used, such as the terpenic solvents including rosinderivatives, aliphatic ketones such as cyclohexanone, and complexalcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiableconcentrates are chosen from conventional nonionic surfactants, such asthose discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds ofthis invention, dispersed in an aqueous vehicle at a concentration inthe range from about 5% to about 50% by weight. Suspensions are preparedby finely grinding the compound, and vigorously mixing it into a vehiclecomprised of water and surfactants chosen from the same types discussedabove. Inert ingredients, such as inorganic salts and synthetic ornatural gums, may also be added, to increase the density and viscosityof the aqueous vehicle. It is often most effective to grind and mix thecompound at the same time by preparing the aqueous mixture, andhomogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

The compounds may also be applied as granular compositions, which areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the compound,dispersed in an inert carrier which consists entirely or in large partof clay or a similar inexpensive substance. Such compositions areusually prepared by dissolving the compound in a suitable solvent andapplying it to a granular carrier which has been pre-formed to theappropriate particle size, in the range of from about 0.5 to 3 mm. Suchcompositions may also be formulated by making a dough or paste of thecarrier and compound and crushing and drying to obtain the desiredgranular particle size.

Dusts containing the compounds are prepared simply by intimately mixingthe compound in powdered form with a suitable dusty agriculturalcarrier, such as kaolin clay, ground volcanic rock, and the like. Dustscan suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply thecompound in the form of a solution in an appropriate organic solvent,usually a bland petroleum oil, such as the spray oils, which are widelyused in agricultural chemistry.

Insecticides, acaricides and fungicides are generally applied in theform of a dispersion of the active ingredient in a liquid carrier. It isconventional to refer to application rates in terms of the concentrationof active ingredient in the carrier. The most widely used carrier iswater.

The compounds of the present invention can also be applied in the formof an aerosol composition. In such compositions the active compound isdissolved or dispersed in an inert carrier, which is apressure-generating propellant mixture. The aerosol composition ispackaged in a container from which the mixture is dispensed through anatomizing valve. Propellant mixtures comprise either low-boilinghalocarbons, which may be mixed with organic solvents, or aqueoussuspensions pressurized with inert gases or gaseous hydrocarbons.

The formulations may additionally contain adjuvant surfactants toenhance deposition, wetting and penetration of the compounds onto thetarget crop and organism. These adjuvant surfactants may optionally beemployed as a component of the formulation or as a tank mix. The amountof adjuvant surfactant will typically vary from 0.01 to 1.0% by volume,based on a spray-volume of water, preferably 0.05 to 0.5 volume %.Suitable adjuvant surfactants include, but are not limited toethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols,salts of the esters or sulphosuccinic acids, ethoxylatedorganosilicones, ethoxylated fatty amines and blends of surfactants withmineral or vegetable oils.

Another aspect of the present invention relates to a method forinhibiting an insect which comprises applying to a locus of the insectan insect-inhibiting amount of a compound of Formula (I).

The “locus” of insects is a term used herein to refer to the environmentin which the insects live or where their eggs are present, including theair surrounding them, the food they eat, or objects which they contact.For example, insects which eat or contact edible or ornamental plantscan be controlled by applying the active compound to plant parts such asthe seed, seedling, or cutting which is planted, the leaves, stems,fruits, grain, or roots, or to the soil in which the roots are growing.It is contemplated that the compounds might also be useful to protecttextiles, paper, stored grain, seeds, domesticated animals, buildings orhuman beings by applying an active compound to or near such objects. Theterm “inhibiting an insect” refers to a decrease in the numbers ofliving insects, or a decrease in the number of viable insect eggs. Theextent of reduction accomplished by a compound depends, of course, uponthe application rate of the compound, the particular compound used, andthe target insect species. At least an inactivating amount should beused. The terms “insect-inactivating amount” are used to describe theamount, which is sufficient to cause a measurable reduction in thetreated insect population. Generally an amount in the range from about 1to about 1000 ppm by weight active compound is used.

The actual amount of compound to be applied to loci of insects and mitesis not critical and can readily be determined by those skilled in theart in view of the examples above. In general, concentrations from 10ppm to 5000 ppm by weight of compound are expected to provide goodcontrol. With many of the compounds, concentrations from 100 to 1500 ppmwill suffice.

The locus to which a compound is applied can be any locus inhabited byan insect or mite, for example, vegetable crops, fruit and nut trees,grape vines, ornamental plants, domesticated animals, the interior orexterior surfaces of buildings, and the soil around buildings.

Another embodiment of the present invention is a method for the controlor prevention of fungal attack. This method comprises applying to thesoil, plant, roots, foliage, seed or locus of the fungus, or to a locusin which the infestation is to be prevented (for example applying tocereal or grape plants), a fungicidal effective amount of one or more ofthe compounds. The compounds are suitable for treatment of variousplants at fungicidal levels, while exhibiting low phytotoxicity. Thecompounds are useful both in a protectant and/or an eradicant fashion.

The compounds have been found to have significant fungicidal effectparticularly for agricultural use. Many of the compounds areparticularly effective for use with agricultural crops and horticulturalplants. It will be understood by those in the art that the efficacy ofthe compound for the foregoing fungi establishes the general utility ofthe compounds as fungicides.

The compounds have broad ranges of efficacy as fungicides. The exactamount of the active material to be applied is dependent not only on thespecific active material being applied, but also on the particularaction desired, the fungal species to be controlled, and the stage ofgrowth thereof, as well as the part of the plant or other product to becontacted with the compound. Thus, all the compounds, and formulationscontaining the same, may not be equally effective at similarconcentrations or against the same fungal species.

The compounds are effective in use with plants in a disease-inhibitingand phytologically acceptable amount. The term “disease inhibiting andphytologically acceptable amount” refers to an amount of a compound thatkills or inhibits the plant disease for which control is desired, but isnot significantly toxic to the plant. This amount will generally be fromabout 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm beingpreferred. The exact concentration of compound required varies with thefungal disease to be controlled, the type of formulation employed, themethod of application, the particular plant species, climate conditions,and the like. A suitable application rate is typically in the range fromabout 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per squaremeter, g/m²).

Additionally, the compounds of the present invention (Formula I) areoften applied in conjunction with one or more other insecticides orfungicides to obtain control of a wider variety of pests and diseases.Such additional pesticidal compounds may be fungicides, insecticides,nematocides, miticides, arthropodicides, bactericides or combinationsthereof that are compatible with the compounds of the present inventionin the medium selected for application, and not antagonistic to theactivity of the present compounds. Accordingly, in such embodiments, theother pesticidal compound is employed as a supplemental toxicant for thesame or for a different pesticidal use. The compounds of Formula I, andthe pesticidal compound in the combination can generally be present in aweight ratio of from 1:100 to 100:1.

When used in conjunction with other insecticides or fungicides, thepresently claimed compounds can be formulated with the otherinsecticides or fungicides, tank mixed with the other insecticides orfungicides, or applied sequentially with the other insecticides orfungicides.

Some of the insecticides that can be employed beneficially incombination with the compounds of the present invention include, but arenot limited to: antibiotic insecticides such as allosamidin andthuringiensin; macrocyclic lactone insecticides such as spinosad;avermectin insecticides such as abamectin, doramectin, emamectin,eprinomectin, ivermectin and selamectin; milbemycin insecticides such aslepimectin, milbemectin, milbemycin oxime and moxidectin; arsenicalinsecticides such as calcium arsenate, copper acetoarsenite, copperarsenate, lead arsenate, potassium arsenite and sodium arsenite;botanical insecticides such as anabasine, azadirachtin, d-limonene,nicotine, pyrethrins, cinerins, cinerin I, cinerin II, jasmolin I,jasmolin II, pyrethrin I, pyrethrin II, quassia, rotenone, ryania andsabadilla; carbamate insecticides such as bendiocarb and carbaryl;benzofuranyl methylcarbamate insecticides such as benfuracarb,carbofuran, carbosulfan, decarbofuran and furathiocarb;dimethylcarbamate insecticides dimitan, dimetilan, hyquincarb andpirimicarb; oxime carbamate insecticides such as alanycarb, aldicarb,aldoxycarb, butocarboxim, butoxycarboxim, methomyl, nitrilacarb, oxamyl,tazimcarb, thiocarboxime, thiodicarb and thiofanox; phenylmethylcarbamate insecticides such as allyxycarb, aminocarb, bufencarb,butacarb, carbanolate, cloethocarb, dicresyl, dioxacarb, EMPC,ethiofencarb, fenethacarb, fenobucarb, isoprocarb, methiocarb,metolcarb, mexacarbate, promacyl, promecarb, propoxur, trimethacarb, XMCand xylylcarb; dinitrophenol insecticides such as dinex, dinoprop,dinosam and DNOC; fluorine insecticides such as bariumhexafluorosilicate, cryolite, sodium fluoride, sodium hexafluorosilicateand sulfluramid; formamidine insecticides such as amitraz,chlordimeform, formetanate and formparanate; fumigant insecticides suchas acrylonitrile, carbon disulfide, carbon tetrachloride, chloroform,chloropicrin, para-dichlorobenzene, 1,2-dichloropropane, ethyl formate,ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogencyanide, iodomethane, methyl bromide, methylchloroform, methylenechloride, naphthalene, phosphine, sulfuryl fluoride andtetrachloroethane; inorganic insecticides such as borax, calciumpolysulfide, copper oleate, mercurous chloride, potassium thiocyanateand sodium thiocyanate; chitin synthesis inhibitors such asbistrifluoron, buprofezin, chlorfluazuron, cyromazine, diflubenzuron,flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron,noviflumuron, penfluoron, teflubenzuron and triflumuron; juvenilehormone mimics such as epofenonane, fenoxycarb, hydroprene, kinoprene,methoprene, pyriproxyfen and triprene; juvenile hormones such asjuvenile hormone I, juvenile hormone II and juvenile hormone III;moulting hormone agonists such as chromafenozide, halofenozide,methoxyfenozide and tebufenozide; moulting hormones such as α-ecdysoneand ecdysterone; moulting inhibitors such as diofenolan; precocenes suchas precocene I, precocene II and precocene III; unclassified insectgrowth regulators such as dicyclanil; nereistoxin analogue insecticidessuch as bensultap, cartap, thiocyclam and thiosultap; nicotinoidinsecticides such as flonicamid; nitroguanidine insecticides such asclothianidin, dinotefuran, imidacloprid and thiamethoxam; nitromethyleneinsecticides such as nitenpyram and nithiazine; pyridylmethylamineinsecticides such as acetamiprid, imidacloprid, nitenpyram andthiacloprid; organochlorine insecticides such as bromo-DDT, camphechlor,DDT, pp′-DDT, ethyl-DDD, HCH, gamma-HCH, lindane, methoxychlor,pentachlorophenol and TDE; cyclodiene insecticides such as aldrin,bromocyclen, chlorbicyclen, chlordane, chlordecone, dieldrin, dilor,endosulfan, endrin, HEOD, heptachlor, HHDN, isobenzan, isodrin, kelevanand mirex; organophosphate insecticides such as bromfenvinfos,chlorfenvinphos, crotoxyphos, dichlorvos, dicrotophos, dimethylvinphos,fospirate, heptenophos, methocrotophos, mevinphos, monocrotophos, naled,naftalofos, phosphamidon, propaphos, TEPP and tetrachlorvinphos;organothiophosphate insecticides such as dioxabenzofos, fosmethilan andphenthoate; aliphatic organothiophosphate insecticides such as acethion,amiton, cadusafos, chlorethoxyfos, chlormephos, demephion, demephion-O,demephion-S, demeton, demeton-O, demeton-S, demeton-methyl,demeton-O-methyl, demeton-S-methyl, demeton-S-methylsulphon, disulfoton,ethion, ethoprophos, IPSP, isothioate, malathion, methacrifos,oxydemeton-methyl, oxydeprofos, oxydisulfoton, phorate, sulfotep,terbufos and thiometon; aliphatic amide organothiophosphate insecticidessuch as amidithion, cyanthoate, dimethoate, ethoate-methyl, formothion,mecarbam, omethoate, prothoate, sophamide and vamidothion; oximeorganothiophosphate insecticides such as chlorphoxim, phoxim andphoxim-methyl; heterocyclic organothiophosphate insecticides such asazamethiphos, coumaphos, coumithoate, dioxathion, endothion, menazon,morphothion, phosalone, pyraclofos, pyridaphenthion and quinothion;benzothiopyran organothiophosphate insecticides such as dithicrofos andthicrofos; benzotriazine organothiophosphate insecticides such asazinphos-ethyl and azinphos-methyl; isoindole organothiophosphateinsecticides such as dialifos and phosmet; isoxazole organothiophosphateinsecticides such as isoxathion and zolaprofos; pyrazolopyrimidineorganothiophosphate insecticides such as chlorprazophos and pyrazophos;pyridine organothiophosphate insecticides such as chlorpyrifos andchlorpyrifos-methyl; pyrimidine organothiophosphate insecticides such asbutathiofos, diazinon, etrimfos, lirimfos, pirimiphos-ethyl,pirimiphos-methyl, primidophos, pyrimitate and tebupirimfos; quinoxalineorganothiophosphate insecticides such as quinalphos andquinalphos-methyl; thiadiazole organothiophosphate insecticides such asathidathion, lythidathion, methidathion and prothidathion; triazoleorganothiophosphate insecticides such as isazofos and triazophos; phenylorganothiophosphate insecticides such as azothoate, bromophos,bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cythioate,dicapthon, dichlofenthion, etaphos, famphur, fenchlorphos, fenitrothionfensulfothion, fenthion, fenthion-ethyl, heterophos, jodfenphos,mesulfenfos, parathion, parathion-methyl, phenkapton, phosnichlor,profenofos, prothiofos, sulprofos, temephos, trichlormetaphos-3 andtrifenofos; phosphonate insecticides such as butonate and trichlorfon;phosphonothioate insecticides such as mecarphon; phenylethylphosphonothioate insecticides such as fonofos and trichloronat;phenyl phenylphosphonothioate insecticides such as cyanofenphos, EPN andleptophos; phosphoramidate insecticides such as crufomate, fenamiphos,fosthietan, mephosfolan, phosfolan and pirimetaphos;phosphoramidothioate insecticides such as acephate, isocarbophos,isofenphos, methamidophos and propetamphos; phosphorodiamideinsecticides such as dimefox, mazidox, mipafox and schradan; oxadiazineinsecticides such as indoxacarb; phthalimide insecticides such asdialifos, phosmet and tetramethrin; pyrazole insecticides such asacetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, tebufenpyrad,tolfenpyrad and vaniliprole; pyrethroid ester insecticides such asacrinathrin, allethrin, bioallethrin, barthrin, bifenthrin,bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin,beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin,cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin,zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin,empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate,esfenvalerate, flucythrinate, fluvalinate, tau-fluvalinate, furethrin,imiprothrin, metofluthrin, permethrin, biopermethrin, transpermethrin,phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin,bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin,tralomethrin and transfluthrin; pyrethroid ether insecticides such asetofenprox, flufenprox, halfenprox, protrifenbute and silafluofen;pyrimidinamine insecticides such as flufenerim and pyrimidifen; pyrroleinsecticides such as chlorfenapyr; tetronic acid insecticides such asspiromesifen; thiourea insecticides such as diafenthiuron; ureainsecticides such as flucofuron and sulcofuron; and unclassifiedinsecticides such as closantel, crotamiton, EXD, fenazaflor, fenoxacrim,flubendiamide, hydramethylnon, isoprothiolane, malonoben, metaflumizone,metoxadiazone, nifluridide, pyridaben, pyridalyl, rafoxanide,triarathene and triazamate and any combinations thereof.

Some of the fungicides that can be employed beneficially in combinationwith the compounds of the present invention include, but are not limitedto: enestrobin, antimycin, quinoxyfen, SYP-048, IK-1140, NC-224,2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, Ampelomyces, quisqualis, azaconazole,azoxystrobin, Bacillus subtilis, benalaxyl, benomyl,benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt,bicarbonates, biphenyl, bismerthiazol, bitertanol, blasticidin-S, borax,Bordeaux mixture, boscalid, bromuconazole, bupirimate, calciumpolysulfide, captafol, captan, carbendazim, carboxin, carpropamid,carvone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans,copper hydroxide, copper octanoate, copper oxychloride, copper sulfate,copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid,cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammoniumethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet,diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion,diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorphacetate, dodine, dodine free base, edifenphos, epoxiconazole, ethaboxam,ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide,ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide,fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide,flutolanil, flutriafol, folpet, formaldehyde, fosetyl,fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine,guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol,imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadinetriacetate, iminoctadine tris(albesilate), ipconazole, iprobenfos,iprodione, iprovalicarb, isoprothiolane, kasugamycin, kasugamycinhydrochloride hydrate, kresoxim-methyl, mancopper, mancozeb, maneb,mepanipyrim, mepronil, mercuric chloride, mercuric oxide, mercurouschloride, metalaxyl, mefenoxam, metalaxyl-M, metam, metam-ammonium,metam-potassium, metam-sodium, metconazole, methasulfocarb, methyliodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone,mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol,octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl,oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate,penconazole, pencycuron, pentachlorophenol, pentachlorophenyl laurate,penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide,picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate,potassium hydroxyquinoline sulfate, probenazole, prochloraz,procymidone, propamocarb, propamocarb hydrochloride, propiconazole,propineb, proquinazid, prothioconazole, pyraclostrobin, pyrazophos,pyributicarb, pyrifenox, pyrimethanil, pyroquilon, quinoclamine,quinoxyfen, quintozene, Reynoutria sachalinensis extract, silthiofam,simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z071, tar oils,tebuconazole, tecnazene, tetraconazole, thiabendazole, thifluzamide,thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid,triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph,trifloxystrobin, triflumizole, triforine, triticonazole, validamycin,vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusariumoxysporum, Gliocladium spp., Phlebiopsis gigantean, Streptomycesgriseoviridis, Trichoderma spp.,(RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme: ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmiumcalcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,chloraniformethan, chlorfenazole, chlorquinox, climbazole, copperbis(3-phenylsalicylate), copper zinc chromate, cufraneb, cuprichydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram,decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol,dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin,drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf,fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole,furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin,halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos,isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam,methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride,myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenyl-itaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb;prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor,pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole,rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor,thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid,triamiphos, triarimol, triazbutil, trichlamide, urbacid, XRD-563, andzarilamid, and any combinations thereof.

EXAMPLES

Throughout the present specification, all temperatures are given indegrees Celsius, and all percentages are weight percentages unlessotherwise stated. The following examples are representative of theembodiments of the present invention and should not be read as limiting.

The compounds of the present invention may be synthesized by methodsthat are individually known to those skilled in the art.

The compounds of Formula I wherein R1, R2, X, Y, are previously definedcan be prepared by the methods illustrated in the following schemes.

In step a, of scheme A, alcohol 1 is treated with methan sulfonylchloride and triethylamine (Et₃N) at 0° C. to yield mesylate 2, whichundergoes a nucleophilic displacement with piperazine in step b, todeliver compound 4. The preferred solvent for the nucleophilicdisplacement is acetonitrile (CH₃CN) and elevated temperatures arerequired to drive the reaction to completion. Commercialmono-substituted piperazines were used directly in schemes B and C whenavailable.

As depicted in step a, a substituted piperazine, 4, is reacted with anacid chloride 5 to yield the appropriately acyl piperazine 6. Theacylation is performed under basic conditions to neutralize thehydrochloric acid (HCl) formed during the reaction; examples of typicalbases are diispropylamine (DIEA) and Et₃N.

As depicted in Scheme C, a substituted piperazine, 4, is reacted withchloro derivative 7 (note bromides can also be used) and heated at 80°C. in dimethylformamide (DMF) to give the appropriately substitutedpiperazine 8. The reaction is performed under basic conditions toneutralize the HCl formed during the reaction; examples of typical basesare DIEA and Et₃N. Alternatively, t-butylcarbamate (BOC) protectedpiperazine can be utilized as illustrated in schemes D and E. In step a,of scheme D, BOC protected piperazine is N-acylated with an acidchloride utilizing similar reactions previously described to yieldcompound 10. The BOC group is removed with trifluoroacetic acid (TFA) inmethylene chloride (CH₂Cl₂) and the free base 11, is N-alkylated, againutilizing reaction conditions described earlier, to yield derivatives of6.

The N-acylation and N-alkylation steps in scheme D can be reversed asshown in scheme E to deliver derivatives of 6.

The following examples further illustrate the present invention, but,are not to be construed as in any way limiting its scope.

Example I 1-Benzyl-4-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperazine(14)

To a 2-dram screw-cap vial was added polymer-supporteddiisopropylethylamine (PS-DIEA, 54 mg, 0.2 mmol based on 3.68 mmol/gloading of resin) and DMF (2 mL). The vials were placed in an orbitalshaker allowed to shake for 15 min. 1-Benzylpiperazine (35 mg, 0.2 mmol)was dissolved in DMF (100 μL) and transferred by pipette to the vial.3,5-Dimethylisoxazole-4-carbonyl chloride (32 mg, 0.2 mmol), wasdissolve in DMF (100 μL) and transferred to the vial. The vial wascapped and allowed to shake at room temperature (RT) for 12 h. Thereaction mixture filtered and solvent evaporated to give the desiredacylated piperazine. MS ELS+ 300.

Example II1-(2-methyoxybenzoyl)-4-{2-[2-trifluoromethyl)phenyl]ethyl}piperazine(15)

1-[2-(Trifluoromethyl)phenethyl]piperazine (200 mg, 0.60 mmol), o-anisylchloride (100 mg, 0.59 mmol), and Et₃N (253 μL, 1.81 mmol) weredissolved in DMF (10 mL) and stirred at ambient temperature for 12 h.The reaction mixture was extracted with diethylether (Et₂O) and thecombined organic layers washed with brine, dried over anhydrous sodiumsulfate (Na₂SO₄) and evaporated to give an amber oil (120 mg, 51%). ¹HNMR (CDCl₃) δ: 2.4-2.7 (m, 6H), 2.9-3.0 (t, 2H), 3.2-3.35 (m, 2H),3.8-3.95 (m, 5H), 6.89-7.01 (m, 2H), 7.22-7.37 (m, 4H), 7.43-7.49 (t,1H), 7.59-7.62 (d, 1H). MS ELS+ 393.

Example III1-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-4-(2-phenoxyethyl)piperazine(16)

1-[2-(phenoxy)-ethyl]piperazine (200 mg, 0.974 mmol), 6-chloropiperonylchloride (200 mg, 0.974 mmol), and Et3N (415 μL, 3 mmol) were combinedin tetrahydrofuran (THF 20 mL). The reaction mixture was heated at 60°C. for 12 h. The reaction mixture was cooled and extracted with ethylacetate (EtOAc). The combined organic layers were washed with brine,dried over anhydrous Na₂SO₄ and evaporated. The crude residue waschromatographed on silica (20% EtOAc/Hexanes) and the product fractionswere collected and evaporated to an amber solid (186 mg, 51%). ¹H NMR(CDCl₃) δ: 2.5-2.7 (m, 8H), 2.8 (t, 2H), 3.5 (s, 2H), 4.1 (t, 2H), 5.9(s, 2H), 6.81 (s, 1H), 6.9-6.94 (m, 3H), 6.96-6.98 (m, 1H), 7.26-7.3 (m,1H). MS ELS+ 376. CHN: calc., 64.08, 6.18, 7.47; found, 63.87, 6.12,7.44. mp: 72-76° C.

Example IV 3-{[4-(2-phenylethyl)piperazin-1-yl]methyl}benzonitrile (17)

To a 2-dram screw-cap vial was added PS-DIEA (54 mg, 0.2 mmol) and DMF(2 mL). The vials were placed in an orbital shaker allowed to shake for15 min. 1-(2-phenylethyl)-piperazine (38 mg, 0.2 mmol was dissolved inDMF (100 mL) and transferred by pipette to the vial.3-Chloromethylbenzonitrile (30 mg, 0.2 mmol), was dissolve in DMF (100mL) and transferred to the vial. The vial was capped and heated at 80°C. with shaking for 12 h. The vial was cooled to RT and the reactionmixture filtered and solvent evaporated to give the desired substitutedpiperazine. MS ELS+ 306.

Intermediate Compound 2-(2,4-dichlorophenyl)ethyl methanesulfonate (18)

To a stirred mixture of 2,4-dichlorophenethylalcohol (955.0 mg, 5.0 mol)at 0° C. was added Et₃N (1.1 mL, 7.5 mmol) and stirred for 5 min.Methane sulfonyl chloride (572.8 mg, 5.0 mmol) was added neat, dropwiseby syringe. A precipitate formed and the reaction mixture stirred 30min. The mixture was filtered, diluted with Et₂O (20 mL) and cooled atto 0° C. After 20 min., the mixture was filtered through a pad ofsilica, dried over anhydrous Na₂SO₄ and evaporated. The crude residuewas co-evaporated with toluene and chloroform (1:1) to give a yellow oil(1.1 g, 80%). The mesylate was used directly in subsequent reactions. ¹HNMR (CDCl₃) δ 2.9 (s, 3H), 3.18 (t, 2H), 4.42 (t, 2H), 7.22 (d, 2H),7.41 (t, 1H).

Intermediate Compound 1-[(2-(2,4-dichlorophenyl)ethyl]piperazine (19)

piperazine (1.9 g, 22 mmol) was stirred in 20 mL CH₃CN at 75° C.Compound 19 (1.1 g, 4.1 mmol) was dissolved in CH₃CN (2 mL) and addeddropwise via syringe. The reaction mixture was heated at 60° C. for 30min. The mixture was poured over ice and extracted with EtOAC. Thecombined organic layers were washed with water, dried over anhydrousmagnesium sulfate (MgSO₄), and evaporated to yield the desiredpiperazine as a yellow oil (826 mg, 80%). ¹H NMR (CDCl₃) δ 2.55 (bm,6H), 2.9 (bm, 6H), 7.19 (d, 2H), 7.36 (t, 1H)

Example V tert-butyl 4-(2-phenylpropanoyl)piperazine-1-carboxylate (20)

To a stirred mixture of 2-phenyl propionic acid (1.0 g, 6.7 mmol) in1,2-dichloroethane (15 mL) was added a few drops of DMF and excessthionyl chloride. The resulting mixture was heated at reflux for 2 h,when bubbling ceased the mixture was evaporated to dryness. The cruderesidue was co-evaporated with toluene and 1,2-dichloroethane. Theresidue was dissolved in CH₂Cl₂ and cooled to 0° C. To the stirredsolution, BOC-piperazine (1.24 g, 6.7 mmol) and Et₃N were added. A whiteprecipitate formed and the reaction was stirred 12 h at RT. Et₂O wasadded and the mixture was washed with water and brine. The ether layerwas separated and dried over anhydrous Na₂SO₄, filtered, and evaporated.The residue was treated with 20% ether/hexanes and the resulting solidfiltered. The filtrate was evaporated and the procedure repeated. Afterdrying, there remained a white solid (1.3 g, 62%). ¹H NMR (CDCl₃) δ: 1.4(s, 9H), 1.42 (d, 3H), 2.7 (m, 1H), 3.1-3.6 (m, 6H), 3.85 (m, 2H),7.2-7.4 (m, 5H). [M+Na] 341.

Example VI1-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-4-(2-phenylpropanoyl)piperazine(21)

To a stirred mixture of compound 201 (500 mg, 1.57 mmol) in CH₂Cl₂ wasadded trifluoroacetic acid TFA (excess). The mixture was stirred 1 h andwas evaporated to dryness. The crude residue was dissolved in DMF and6-chloropiperonyl chloride (321 mg, 1.57 mmol), and Et₃N were added. Thereaction mixture was stirred at 80° C. for 3 h after which the mixturewas poured into water and extracted with Et₂O. The combined Et₂O layerswere washed with water, brine and dried over anhydrous Na₂SO₄, filtered,and evaporated to give orange oil (500 mg, 83%). ¹H NMR (CDCl₃) δ: 1.42(d, 3H), 1.95 (m, 1H), 2.25-2.5 (m, 3H), 3.2-3.8 (bm, 4H), 3.41 (s, 2H),3.85 (q, 1H), 5.95 (s, 2H), 6.79 (s, 1H), 6.9 (s, 1H), 7.2-7.35 (m, 5H).

Example VII1-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-4-(2-phenylpropyl)piperazine(22)

To a stirred mixture of compound 21 (200, mg 0.52 mmol) in THF (7.0 mL)was added lithium aluminum hydride (LAH) (0.4 mL of 1M in THF). Themixture was refluxed for 1 h. To the cooled mixture was added ice-waterto quench unreacted LAH. The mixture was stirred 1 h and extracted withEt₂O and the combined organic layers were washed with brine, dried overanhydrous Na₂SO₄, and evaporated. The crude residue was purified viaflash column (20% EtOAc/Hexanes) and the product fractions evaporated togive an orange oil (179.8 mg, 93%). 1H NMR (CDCl₃) δ: 1.15 (d, 3H),2.35-2.55 (bm, 10H), 2.9 (m, 1H), 3.5 (s, 2H), 5.98 (s, 2H), 6.8 (s,1H), 6.95 (s, 1H) 7.18-7.35 (m, 5H). GC-MS: calcd, 372; found, 372.

TABLE 1 lists compounds of the invention prepared according to theprocedures described in Scheme A-D as well as illustrated by ExamplesI-VII.

TABLE 1 Compound # Structure Characterization 23

[M + H]+: 288 24

[M + H]+: 306 25

[M + H]+: 294 26

[M + H]+: 355 27

[M + H]+: 343 28

[M + H]+: 316 29

[M + H]+: 304 30

[M + H]+: 325 31

[M + H]+: 313 32

[M + H]+: 282 33

[M + H]+: 270 34

[M + H]+: 271 35

[M + H]+: 259 36

[M + H]+: 295 37

[M + H]+: 283 38

[M + H]+: 329, 331 39

[M + H]+: 317 40

[M + H]+: 311 41

[M + H]+: 299 42

[M + H]+: 306 43

[M + H]+: 294 44

[M + H]+: 315, 317 45

[M + H]+: 303 46

[M + H]+: 339 47

[M + H]+: 327 48

[M + H]+: 299 49

[M + H]+: 287 50

[M + H]+: 321 51

[M + H]+: 309 52

[M + H]+: 301 53

[M + H]+: 289 54

[M + H]+: 261 55

[M + H]+: 249 56

[M + H]+: 309 57

[M + H]+: 331, 333 58

[M + H]+: 393 59

[M + H]+: 339 60

[M + H]+: 407 61

[M + H]+: 353 62

[M + H]+: 339 63

[M + H]+: 369 64

[M + H]+: 437 65

[M + H]+: 383 66

[M + H]+: 391 67

[M + H]+: 413 68

[M + H]+: 359 69

[M + H]+: 345 70

[M + H]+: 375 71

[M + H]+: 326 72

[M + H]+: 396 73

[M + H]+: 345 74

[M + H]+: 360 75

[M + H]+: 407 76

[M + H]+: 353 77

[M + H]+: 353 78

[M + H]+: 299 79

[M + Na]: 337 80

[M + H]+: 399 81

[M + H]+: 389 82

[M + H]+: 383 83

[M + H]+: 384, 386 84

[M + H]+: 329 85

[M + H]+: 315 86

[M + H]+: 427, 430 87

[M + H]+: 407 88

[M + H]+: 439 89

[M + H]+: 386 90

[M + H]+: 339 91

[M + H]+: 365 92

[M + H]+: 373 93

[M + H]+: 357 94

[M + H]+: 345 95

[M + H]+: 413 96

[GC-MS]: 357 97

[M + H]+: 407 98

[M + H]+: 393 99

[M + H]+: 454 100

[M + H]+: 407 101

[GC-MS]: 382 102

[GC-MS]: 364 103

[M + H]+: 375 104

[GC-MS]: 358 105

[M + H]+: 405 106

[GC-MS]: 358 107

[GC-MS]: 3927 108

[M + H]+: 443 109

[M + H]+: 355 110

[M + H]+: 358 111

[M + H]+: 403 112

[M + H]+: 387 113

[M + H]+: 421 114

[M + H]+: 351 115

[M + H]+: 437 116

[M + H]+: 369 117

[M + H]+: 315 118

[M + H]+: 345 119

[M + H]+: 414 120

[M + H]+: 369 121

[M + H]+: 315 122

[M + H]+: 301 123

[M + H]+: 331 124

[M + H]+: 381 125

[M + H]+: 327 126

[M + H]+: 446 127

[M + H]+: 339 128

[M + H]+: 385 129

[M + H]+: 380 130

[M + H]+: 368 131

[M + H]+: 299 132

[M + H]+: 366 133

[M + H]+: 288 134

[M + H]+: 305 135

[M + H]+: 287 136

[M + H]+: 275 137

[M + H]+: 300 138

[M + H]+: 297 139

[M + H]+: 355 140

[M + H]+: 398 141

[M + H]+: 330 142

[M + H]+: 285 143

[M + H]+: 475 144

[M + H]+: 407 145

[M + H]+: 301 146

[M + H]+: 331 147

[M + H]+: 313 148

[M + H]+: 343 149

[M + H]+: 378 150

[M + H]+: 392 151

[M + H]+: 378 152

[M + H]+: 408 153

[M + H]+: 410 154

[M + H]+: 356 155

[M + H]+: 342 156

[M + H]+: 414 157

[M + H]+: 360 158

[M + H]+: 346 159

[M + H]+: 376 160

[M + H]+: 437 161

[M + H]+: 382 162

[M + H]+: 369 163

[M + H]+: 399 164

[M + H]+: 368 165

[M + H]+: 314 166

[M + H]+: 300 167

[M + H]+: 405 168

[M + H]+: 351 169

[M + H]+: 337 170

[M + H]+: 367 171

[M + H]+: 349 172

[M + H]+: 335 173

[M + H]+: 365 174

[M + H]+: 371 175

[M + H]+: 317 176

[M + H]+: 303 177

[M + H]+: 333 178

[M + H]+: 379 179

[M + H]+: 311 180

[M + H]+: 341 181

[M + H]+: 353 182

[M + H]+: 369 183

[M + H]+: 437 184

[M + H]+: 383 185

[M + H]+: 369 186

[M + H]+: 399 187

[M + H]+: 331 188

[M + H]+: 361 189

[M + H]+: 312 190

[M + H]+: 330 191

[M + H]+: 316 192

[M + H]+: 346 193

[M + H]+: 365 194

[M + H]+: 351 195

[M + H]+: 381 196

[M + H]+: 373 197

[M + H]+: 359 198

[M + H]+: 389 199

[M + H]+: 353 200

[M + H]+: 369 201

[M + H]+: 417 202

[M + H]+: 349 203

[M + H]+: 379 204

[M + H]+: 447 205

[M + H]+: 393 206

[M + H]+: 379 207

[M + H]+: 409 208

[M + H]+: 261 209

[M + H]+: 368 210

[M + H]+: 314 211

[M + H]+: 300 212

[M + H]+: 330 213

[M + H]+: 323 214

[M + H]+: 309 215

[M + H]+: 339 216

[M + H]+: 383 217

[M + H]+: 329 218

[M + H]+: 315 219

[M + H]+: 345 220

[M + H]+: 335 221

[M + H]+: 321 222

[M + H]+: 351 223

[M + H]+: 397 224

[M + H]+: 343 225

[M + H]+: 329 226

[M + H]+: 359 227

[M + H]+: 400 228

[M + H]+: 346 229

[M + H]+: 332 230

[M + H]+: 362 231

[M + H]+: 348 232

[M + H]+: 364 233

[M + H]+: 360 234

[M + H]+: 346 235

[M + H]+: 376 236

[M + H]+: 371 237

[M + H]+: 401 238

[M + H]+: 277 239

[M + H]+: 302 240

[M + H]+: 290 241

[M + H]+: 310 242

[M + H]+: 308 243

[M + H]+: 388 244

[M + H]+: 386 245

[M + H]+: 307 246

[M + H]+: 305 247

[M + H]+: 307 248

[M + H]+: 332 249

[M + H]+: 340 250

[M + H]+: 338 251

[M + H]+: 358 252

[M + H]+: 346 253

[M + H]+: 364 254

[M + H]+: 294 255

[M + H]+: 293 256

[M + H]+: 318 257

[M + H]+: 324 258

[M + H]+: 309 259

[M + H]+: 334 260

[M + H]+: 322 261

[M + H]+: 342 262

[M + H]+: 340 263

[M + H]+: 347 264

[M + H]+: 372 265

[M + H]+: 360 266

[M + H]+: 380 267

[M + H]+: 378 268

[M + H]+: 354 269

[M + H]+: 379 270

[M + H]+: 387 271

[M + H]+: 387 272

[M + H]+: 353 273

[M + H]+: 378 274

[M + H]+: 366 275

[M + H]+: 386 276

[M + H]+: 384 277

[M + H]+: 333 278

[M + H]+: 358 279

[M + H]+: 346 280

[M + H]+: 366 281

[M + H]+: 364 282

[M + H]+; 325 283

[M + H]+: 350 284

[M + H]+: 338 285

[M + H]+: 356 286

[M + H]+: 299 287

[M + H]+: 324 288

[M + H]+: 312 289

[M + H]+: 332 290

[M + H]+: 330 291

[M + H]+: 293 292

[M + H]+: 318 293

[M + H]+: 326 294

[M + H]+: 324 295

[M + H]+: 262 296

[M + H]+: 325 297

[M + H]+: 309 298

[M + H]+: 273 299

[M + H]+: 340 300

[M + H]+: 324 301

[M + H]+: 322 302

[M + H]+: 270 303

[M + H]+: 355 304

[M + H]+: 303 305

[M + H]+: 381 306

[M + H]+: 329 307

[M + H]+: 311 308

[M + H]+: 295 309

[M + H]+: 259 310

[M + H]+: 341 311

[M + H]+: 325 312

[M + H]+: 357 313

[M + H]+: 341 314

[M + H]+: 395 315

[M + H]+: 379 316

[M + H]+: 343 317

[M + H]+: 402 318

[M + H]+: 350 319

[M + H]+: 401 320

[M + H]+: 385 321

[M + H]+: 349 322

[M + H]+: 381 323

[M + H]+: 365 324

[M + H]+: 329 325

[M + H]+: 321 326

[M + H]+: 347 327

[M + H]+: 331 328

[M + H]+: 295 329

[M + H]+: 34 330

[M + H]+: 325 331

[M + H]+: 289 332

[M + H]+: 421 333

[M + H]+: 373 334

[M + H]+: 422

Example VIII Insecticidal Testing

The compounds identified in TABLE 2 were prepared using the proceduresillustrated in the previous examples and these compounds were testedagainst beet armyworm, mosquito, fruit fly, and cotton aphid usingprotocols described after.

TABLE 2 Compound # LAPHEG AEDSAE DROSME CA 200 17 C C B C 34 C C C D 38C C C A 44 C C C C 50 C C C A 80 B C C B 81 C C C A 86 C B C A 87 C C CB 88 C C C A 90 C C B A 91 C C B C 92 C C B C 93 C C B C 95 C C B A 96 BC C A 99 C C C A 100 C C B A 101 C C C A 102 C C C A 103 C C C A 104 C CA A 105 C C C A 106 C C C A 107 C C A A 108 C C C A 126 C C C A 139 B CC D 146 C C C D 156 C C C A 159 C C C D 160 C C C C 162 C C B D 192 C CC D 303 C C B D 321 C C C D 333 C C A A LAPHEG refers to % mortality at4000 μg/ml against beet armyworm on artificial diet, AEDSAE refers to %mortality at 20 μg/ml against mosquito larvae DROSME refers to %mortality at 4000 μg/ml against adult fruit fly on artificial diet CA200 refers to % control at 200 ppm against cotton aphid in foliar spraytests.

In each case of Table 2 the rating scale is as follows:

% Mortality Rating 50-100 A 26-49  B 1-25 C Not tested D

Insecticidal Tests

Compounds were evaluated on mosquito (Aedes aegypti) larvae, beetarmyworm (Spodoptera exigua) larvae, fruit fly (Drosophila melanogaster)adults and cotton aphid (Aphis gossypi). Newly hatched mosquito larvae(about 50 larvae/well) in 96-well microtiter plates in 230 ul of watercontaining powdered liver/yeast extract (1 gr/100 ml) were treated with20 ppm solution of the test compound. Following treatment the plateswere covered with a lid and mortality was determined three days aftertreatment. Beet armyworm eggs (about 5 per well) were placed onartificial diet (in a 96-well microtiter plate) treated with a 4000 ppmsolution of a test compound in combination with piperonyl butoxide (inapproximate ratio of 1:4). After infestation, the plates were coveredwith a lid and mortality was determined seven days following treatment.Five-day old fruit fly adults (about 5/well) were placed in deep-wellmicrotiter plates containing 250 ul/well of a 2% agar-10% sucrosemixture that had been treated with a 4000 ppm solution of a testcompound. Following infestation, the plates were covered with a lid andmortality was determined three days after treatment. Treatments for themosquito and armyworm were replicated six times each, that of the fruitfly three times each.

Squash with fully expanded cotyledon leaves were trimmed to onecotyledon per plant and infested with cotton aphid (wingless adult andnymph) 1 day prior to chemical application.

Each plant is examined before chemical application to ensure properinfestation (ca. 30-70 aphids per plant). Compounds (3 mg) weredissolved in 3 mL of acetone:methanol (50:50) solvent, forming stocksolutions of 1000 ppm. The stock solutions were then diluted with 0.025%Tween 20 (in H₂O) to make 200 spray solutions. A hand-held Devilbisssprayer was used to apply the spray solutions until runoff to both sidesof the squash cotyledon leaves. Four plants (4 replications) were usedfor each concentration of each compound. Reference plants (solventcheck) were sprayed with 0.025% Tween 20 only. Treated plants were heldin a holding room for 3 days at approximately 23° C. and 40% RH beforethe number of live aphids on each plant was recorded. Insecticidalactivity was measured by Corrected % Control using Abbott's correctionformula and presented in TABLE 2:

Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants        -   Y=No. of live aphids on treated plants

Example IX Fungicidal Testing

The compounds identified in Table 4 were prepared using the proceduresillustrated in the previous examples and these compounds were testedagainst wheat glume blotch and wheat leaf blotch using the protocolsdescribed herein.

Fungicidal Test for LEPTNO

Glume Blotch of Wheat (causal agent Leptosphaeria nodorum=Stagnosporanodorum; Bayer code LEPTNO): Wheat plants (variety Yuma) were grown fromseed in a 50 pasteurized soil/50 percent soil-less mix until theseedlings had a fully expanded first leaf. Each pot contained 3-20seedlings. These plants were sprayed until wet with the formulated testcompound at a rate of 25 ppm. On the following day, the leaves wereinoculated with an aqueous spore suspension of Leptosphaeria nodorum andthe plants were kept in high humidity (one day in a dark dew chamberfollowed by four to seven days in a lighted dew chamber) to permitspores to germinate and infect the leaf. The plants were thentransferred to a greenhouse until disease developed on untreated controlplants.

Fungicidal Test for SEPTTR

Speckled Leaf Blotch of Wheat (Mycosphaerella graminicola=Septoriatritici; Bayer code SEPTTR): Wheat plants (variety Monon) were grownfrom seed in a greenhouse in 50% pasteurized soil/50% soil-less mixuntil the first true leaf was fully expanded, with 3-8 seedlings perpot. These plants were sprayed until wet with the formulated testcompound at a rate of 25 ppm. On the following day, the leaves wereinoculated with an aqueous spore suspension of Septoria tritici and theplants were kept in high humidity (one day in a dark dew chamberfollowed by four to seven days in a lighted dew chamber) to permitspores to germinate and infect the leaf The plants were then transferredto a greenhouse until disease developed on untreated control plants.

TABLE 3 Compound # LEPTNO SEPTTR 80 A A 81 A A 88 C A 92 A C 93 C A 109C A 110 C A 111 A A 112 C A 114 C A 118 A A 119 A B 128 A A 187 A A 234A C 236 A C LETPNO refers to in vitro control one day protectant at 25ppm on wheat glume blotch SEPTTR refers to in vitro control one dayprotectant at 25 ppm on wheat leaf blotch

In each case of TABLE 3 the rating scale is as follows:

% Control Rating 50-100 A 26-49  B 1-25 C

1. A composition comprising a compound of the Formula (I)

wherein X and Y are each independently selected from the groupconsisting of a direct bond, alkyl, carbonyl, carbonylalkyl,carbonylalkylether, carboxylalkyl, alkylcarbonyl, alkylcarboxyl, andalkylether; with the proviso that both X and Y cannot be a direct bond;and when either X or Y is a direct bond, then the R1 or R2 associatedwith that bond is not phenyl or optionally substituted phenyl; and R1and R2 are each independently selected from the group consisting of:alkyl; aryl, optionally substituted with cyano, alkoxy, halogen,alkylhalo, alkoxyhalo, carboxylalkyl, carbonylalkyl, benzyloxy, nitro,benzoyl, phenyl, carboxamido, or heteroaryl; heteroaryl, optionallysubstituted with aryl, heteroaryl, alkyl, halogen, alkylhalo, alkoxy,cycloalkyl or cyano; cycloalkyl, optionally substituted with alkyl orhalogen; and a heterocyclic ring, optionally substituted with alkyl in amixture with one or more fungicides or insecticides or both.
 2. Acomposition according to claim one wherein each of X and Y of saidcompound of Formula (I) are independently selected from the groupconsisting of a direct bond, alkyl, and carbonyl.
 3. A compositionaccording to claim one wherein each of R1 and R2 of said compound ofFormula (I) are independently selected from the group consisting of:alkyl; aryl, optionally substituted with cyano, alkoxy, halogen,alkylhalo, alkoxyhalo, carboxylalkyl, carbonylalkyl, benzyloxy, nitro,benzoyl, phenyl, carboxamido, or heteroaryl; and heteroaryl, optionallysubstituted with aryl, heteroaryl, alkyl, halogen, alkylhalo, alkoxy,cycloalkyl or cyano.
 4. A method of controlling insects comprisingapplying to a locus where control is desired an insect-inactivatingamount of a composition of claim
 1. 5. A method for controlling orpreventing fungal attack comprising applying to the soil, plant, roots,foliage, seed or locus of the fungus, or to a locus in which theinfestation is to be prevented, a fungicidal effective amount of acomposition of claim
 1. 6. A composition according to claim 1 whereinsaid compound of Formula (I) is one of the compounds 1 through 334.